THC + CBD and Memory Study
Primary Purpose
Marijuana Use, Cannabis Use, Cannabis Intoxication
Status
Not yet recruiting
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
High THC/No CBD Marihuana
High THC/High CBD Marihuana
No THC/No CBD Marihuana
Sponsored by
About this trial
This is an interventional other trial for Marijuana Use focused on measuring marijuana, cannabidiol, memory, THC, cannabis, intoxication, MRI, glutamate, MRS
Eligibility Criteria
Inclusion Criteria:
- Right-handed
- Prior MJ users (has used MJ at least once in the past year, but no more than 1x/month in the past 12 months)
- Medically healthy (as determined by medical history and treatment)
- Adequate comprehension of English in order to complete study materials
- Acceptable birth control method for women (i.e., no copper IUD or any device that is not MRI safe)
Exclusion Criteria:
- Participant currently uses psychoactive medications or substances
- Psychiatric diagnoses (determined by DSM-V)
- Participant heavily or regularly uses MJ (more than 1x/month in the past year)
- Current or past substance dependence (including MJ)
- Positive urine toxicology screens
- Positive pregnancy screens
- MRI contraindications (e.g., heart pacemaker)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Occasional Users - High THC and High CBD Dose
Occasional Users - High THC and No CBD Dose
Occasional Users - No THC and No CBD Dose
Arm Description
People who smoke marijuana occasionally will be given a dose of high THC high CBD marijuana at the study visit
People who smoke marijuana occasionally will be given a dose of high THC and no CBD marijuana at the study visit
People who smoke marijuana occasionally will be given a dose of marijuana that contains no THC or CBD
Outcomes
Primary Outcome Measures
fMRI response
Blood oxygen level dependent functional magnetic resonance imaging (fMRI) response during the relational and item specific encoding task. fMRI response will be evaluated during the encoding phase (relational vs. item encoding), item recognition phase (hits vs. misses for item-specific encoding, and hits vs. misses for relational encoding), and associative recognition phase (hits vs. misses).
Glutamate
Magnetic resonance spectroscopy (MRS)-acquired glutamate containing compounds (Glx).
Secondary Outcome Measures
HVLT-R performance
The Hopkins Verbal Learning Test-Revised will ascertain verbal list learning and immediate and delayed recall (~15min); alternate forms have been validated, and the order of versions participants receive will be randomized
Performance on CHARLIE cognitive task
This is a computer-based cognitive battery that administers the Digit Span and Letter/Number Sequencing Test (working memory) and the Digit Symbol Coding test (processing speed). It should take about 10 minutes to complete.
Blood THC and CBD concentration testing
A blood sample will be taken once per dose visit to assess the concentration of the following metabolites in ng/mL: delta-9-tetrahydrocannabinol, 11-hydroxy-tetrahydrocannabinol, 11-Nor-9-Carboxy-tetrahydrocannabinol (THCCOOH), tetrahydrocannabinol-Glucuronide, THCCOOH-Glucuronide, cannabinol (CBN), and cannabidiol (CBD).
Subjective effects on drug effects questionnaire
This self-report will be used to assess subjective reports every 60 minutes throughout the dose visit days. These subjective ratings will be obtained using rapidly completed Visual Analog Scales (VASs) scored on a 0-100 scale. Items include: Do you feel a drug effect right now?, Are you high right now?, Do you dislike any of the effects you are feeling right now?, Do you like any of the effects you are feeling right now? and Would you like more of the drug you took, right now?
Full Information
NCT ID
NCT04855526
First Posted
April 19, 2021
Last Updated
January 4, 2022
Sponsor
Hartford Hospital
Collaborators
Yale University
1. Study Identification
Unique Protocol Identification Number
NCT04855526
Brief Title
THC + CBD and Memory Study
Official Title
Effects of Marijuana on Memory-Related Neurochemistry and Neural Response
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2022 (Anticipated)
Primary Completion Date
June 30, 2022 (Anticipated)
Study Completion Date
June 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hartford Hospital
Collaborators
Yale University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Memory deficits are one of the most consistently observed cognitive effects of marijuana use. There is evidence that some decrements attributable to the primary psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), may be attenuated by cannabidiol (CBD). This study will help us learn more about the relationship between THC and CBD consumption with memory processes. A combination of MRI and neuropsychological tests (which are computer and paper/pencil tasks) will be used to measure the neurocognitive and behavioral impacts of THC and CBD use.
Detailed Description
With increased legalization and medicalization of marijuana (MJ), there is an urgent need to understand the acute effects of use. One of the most consistently observed cognitive outcomes associated with MJ use is memory dysfunction, which may have a substantial impact on daily life in individuals using MJ for recreational or medicinal purposes. Notably, there are numerous preparations of MJ with varying proportions of cannabinoids, which may differ in behavioral and cognitive effects. For instance, there is emerging evidence that acute administration of delta-9-tetrahydrocannabinol (THC), the main psychoactive constituent of MJ, hinders memory and reduces prefrontal and hippocampal functional magnetic resonance imaging (fMRI) activation, but cannabidiol (CBD) may mitigate some of these impairments. Given the role of glutamate in learning and memory, the investigators suggest that these effects may be subserved, in part, by glutamatergic mechanisms. The investigators will use magnetic resonance spectroscopy (MRS) to non-invasively measure glutamate in order to explore the neurochemical underpinnings of memory-related fMRI response changes following acute administration of THC and CBD in a randomized, double-blind, placebo-controlled, cross-over design. A total of 9 healthy participants ages 18-40 will be enrolled. Participants will first undergo one screening visit (~4 hours), comprising informed consent, assessment of health history, psychiatric diagnoses, cognitive function, and substance use history, and a structural MRI session. This will be followed by 3 separate MJ dose visits (~4 hours each), at which participants will complete neuroimaging after administration of one of 3 preparations of vaporized MJ in a randomized, counterbalanced, double-blinded fashion: 1) high THC and no CBD (THC), 2) high THC and high CBD (THC+CBD), and 3) no THC and no CBD (placebo MJ). As in the investigator's ongoing studies, bulk MJ plant material will be provided by the National Institute on Drug Abuse. MJ dose visits will comprise MJ administration, blood collection, MRS/fMRI scan, subjective reports, and a brief cognitive assessment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Marijuana Use, Cannabis Use, Cannabis Intoxication
Keywords
marijuana, cannabidiol, memory, THC, cannabis, intoxication, MRI, glutamate, MRS
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
9 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Occasional Users - High THC and High CBD Dose
Arm Type
Experimental
Arm Description
People who smoke marijuana occasionally will be given a dose of high THC high CBD marijuana at the study visit
Arm Title
Occasional Users - High THC and No CBD Dose
Arm Type
Experimental
Arm Description
People who smoke marijuana occasionally will be given a dose of high THC and no CBD marijuana at the study visit
Arm Title
Occasional Users - No THC and No CBD Dose
Arm Type
Experimental
Arm Description
People who smoke marijuana occasionally will be given a dose of marijuana that contains no THC or CBD
Intervention Type
Drug
Intervention Name(s)
High THC/No CBD Marihuana
Intervention Description
high THC (65 mg THC) and no CBD (0 mg CBD)
Intervention Type
Drug
Intervention Name(s)
High THC/High CBD Marihuana
Intervention Description
high THC (65 mg THC) and high CBD (50 mg CBD)
Intervention Type
Drug
Intervention Name(s)
No THC/No CBD Marihuana
Intervention Description
no THC (0 mg THC) and no CBD (0 mg CBD); placebo drug
Primary Outcome Measure Information:
Title
fMRI response
Description
Blood oxygen level dependent functional magnetic resonance imaging (fMRI) response during the relational and item specific encoding task. fMRI response will be evaluated during the encoding phase (relational vs. item encoding), item recognition phase (hits vs. misses for item-specific encoding, and hits vs. misses for relational encoding), and associative recognition phase (hits vs. misses).
Time Frame
approximately 1 hour following drug administration
Title
Glutamate
Description
Magnetic resonance spectroscopy (MRS)-acquired glutamate containing compounds (Glx).
Time Frame
approximately 1 hour following drug administration
Secondary Outcome Measure Information:
Title
HVLT-R performance
Description
The Hopkins Verbal Learning Test-Revised will ascertain verbal list learning and immediate and delayed recall (~15min); alternate forms have been validated, and the order of versions participants receive will be randomized
Time Frame
Approximately 2.50 hours after drug administration
Title
Performance on CHARLIE cognitive task
Description
This is a computer-based cognitive battery that administers the Digit Span and Letter/Number Sequencing Test (working memory) and the Digit Symbol Coding test (processing speed). It should take about 10 minutes to complete.
Time Frame
Approximately 3.00 hours after drug administration
Title
Blood THC and CBD concentration testing
Description
A blood sample will be taken once per dose visit to assess the concentration of the following metabolites in ng/mL: delta-9-tetrahydrocannabinol, 11-hydroxy-tetrahydrocannabinol, 11-Nor-9-Carboxy-tetrahydrocannabinol (THCCOOH), tetrahydrocannabinol-Glucuronide, THCCOOH-Glucuronide, cannabinol (CBN), and cannabidiol (CBD).
Time Frame
Immediately after drug administration (~0.25 hours after drug administration)
Title
Subjective effects on drug effects questionnaire
Description
This self-report will be used to assess subjective reports every 60 minutes throughout the dose visit days. These subjective ratings will be obtained using rapidly completed Visual Analog Scales (VASs) scored on a 0-100 scale. Items include: Do you feel a drug effect right now?, Are you high right now?, Do you dislike any of the effects you are feeling right now?, Do you like any of the effects you are feeling right now? and Would you like more of the drug you took, right now?
Time Frame
Post drug administration at: 0.00 hours (immediately after); 1.0 hours; 2.0 hours; 3.0 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Right-handed
Prior MJ users (has used MJ at least once in the past year, but no more than 1x/month in the past 12 months)
Medically healthy (as determined by medical history and treatment)
Adequate comprehension of English in order to complete study materials
Acceptable birth control method for women (i.e., no copper IUD or any device that is not MRI safe)
Exclusion Criteria:
Participant currently uses psychoactive medications or substances
Psychiatric diagnoses (determined by DSM-V)
Participant heavily or regularly uses MJ (more than 1x/month in the past year)
Current or past substance dependence (including MJ)
Positive urine toxicology screens
Positive pregnancy screens
MRI contraindications (e.g., heart pacemaker)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chelsea N Meagher, BA
Phone
860-545-7106
Email
chelsea.meagher@hhchealth.org
First Name & Middle Initial & Last Name or Official Title & Degree
Diana G King, BA
Phone
860-545-7563
Email
diana.king@hhchealth.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Godfrey Pearlson, MD
Organizational Affiliation
Hartford Hospital - Olin Neuropsychiatry Research Center; Yale University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alecia Dager, PhD
Organizational Affiliation
Hartford Hospital - Olin Neuropsychiatry Research Center; Yale University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael Stevens, PhD
Organizational Affiliation
Hartford Hospital - Olin Neuropsychiatry Research Center
Official's Role
Principal Investigator
12. IPD Sharing Statement
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THC + CBD and Memory Study
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